Chimeric antigen receptor (CAR) T-cell therapy demonstrates efficacy for the treatment of hematologic cancers, but remains challenging in solid tumors because of the hostile tumor microenvironment and heterogeneity that restrict the infiltration and activity of CAR T-cells. The lack of clinical imaging methods to monitor CAR T-cell therapy in patients limits the potential to enhance the therapeutic approach and predict patient response. Here, a straightforward, non-invasive method for Magnetic Resonance Imaging (MRI) tracking and magnetic targeting of CAR T-cells to enhance T-cell trafficking to solid tumors, in a setting that can be deployed in clinics, is reported. Iron oxide nanoparticles are loaded into T-cells, allowing MRI detection and magnetic cell guidance, while preserving T-cell viability, functions, and CAR specificity to target epidermal growth factor receptor (EGFR)-expressing tumors. Longitudinal MRI monitoring of T-cells over 14 days reveals differences in tumor infiltration rates and antitumor efficacy between EGFR-targeted CAR T-cells and non-transduced T-cell. Moreover, an external magnet placed over the tumor enhances the infiltration of CAR T-cells and increases their antitumor effect. MRI monitoring and magnetic guidance represent a dual-pronged clinically feasible therapeutic strategy to control and promote CAR T-cells delivery into solid tumors, thereby improving the precision, efficacy, and safety of the treatment.

中文翻译：

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CAR T 细胞向实体瘤的体内监测和磁增强递送


嵌合抗原受体 (CAR) T 细胞疗法显示出治疗血液癌症的功效，但由于恶劣的肿瘤微环境和异质性限制了 CAR T 细胞的浸润和活性，因此在实体瘤中仍然具有挑战性。缺乏监测患者 CAR T 细胞治疗的临床成像方法限制了增强治疗方法和预测患者反应的潜力。在此，报告了一种简单、非侵入性的方法，用于磁共振成像 (MRI) 跟踪和 CAR T 细胞的磁性靶向，以增强 T 细胞向实体瘤的运输，并且可以在临床中部署。将氧化铁纳米粒子装载到 T 细胞中，允许 MRI 检测和磁性细胞引导，同时保留 T 细胞的活力、功能和 CAR 特异性，以靶向表达表皮生长因子受体 (EGFR) 的肿瘤。对 T 细胞超过 14 天的纵向 MRI 监测揭示了 EGFR 靶向 CAR T 细胞和非转导 T 细胞之间的肿瘤浸润率和抗肿瘤功效的差异。此外，放置在肿瘤上的外部磁铁可以增强 CAR T 细胞的浸润并增强其抗肿瘤效果。 MRI监测和磁引导代表了一种临床上可行的双管齐下的治疗策略，可以控制和促进CAR T细胞输送到实体瘤中，从而提高治疗的精度、有效性和安全性。